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RNAi-Based Therapy: Prospect as Cancer Treatment
Abstract
Cancer is one of the deadliest form of diseases in humans, with the annual deaths ranging in the millions. Conventional treatments including chemotherapy, radiotherapy, or surgery has their limitations, including common off-target and non-specific effects. Ribonucleic acid interference (RNAi) offers a new strategy for treating cancer by silencing specific genes to prevent gene expression. This review highlights the application of RNAi-based approach in targeting cancer, discusses its potential advantages and limitations, summarizes the existing clinical trials and provides a greater understanding of RNAi-based therapy in cancer.
Keywords
DOI: http://dx.doi.org/10.19166/med.v13i2.8110
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1. World Health Organization (WHO). Fact Sheets: Cancer [Internet]. World Health Organization. World Health Organization. 2022. https://www.who.int/news-room/fact-sheets/detail/cancer
2. Bray F, Jemal A, Torre LA, Forman D, Vineis P. Long-term realism and cost-effectiveness: primary prevention in combating cancer and associated inequalities worldwide. J Natl Cancer Inst. 2015;107(12). https://doi.org/10.1093/jnci/djv273
3. Agrawal N, Dasaradhi PV, Mohmmed A, Malhotra P, Bhatnagar RK, Mukherjee SK. RNA interference: Biology, mechanism, and applications. Microbiol Mol Biol Rev. 2003;67(4):657–85. https://doi.org/10.1128/mmbr.67.4.657-685.2003
4. Kim Y-K. RNA therapy: rich history, various applications and unlimited future prospects. Exp Mol Med. 2022;54(4):455–65. https://doi.org/10.1038%2Fs12276-022-00757-5
5. Svoboda P. Key mechanistic principles and considerations concerning RNA interference. Front Plant Sci. 2020;11.
6. Wang Y. Delivery systems for RNA interference therapy: Current technologies and limitations. Curr Gene Ther. 2020;20(5):356–72. https://doi.org/10.2174/1566523220666201005110726
7. Neumeier J, Meister G. siRNA specificity: RNAi mechanisms and strategies to reduce off-target effects. Front Plant Sci. 2021;11. https://doi.org/10.3389/fpls.2020.526455
8. Chen X, Mangala LS, Rodriguez-Aguayo C, Kong X, Lopez-Berestein G, Sood AK. RNA interference-based therapy and its delivery systems. Cancer and Metastasis Rev. 2017;37(1):107–24. https://doi.org/10.1007/s10555-017-9717-6
9. Tian Z, Liang G, Cui K, Liang Y, Wang Q, Lv S, et al. Insight into the prospects for RNAi therapy of cancer. Front Pharmacol. 2021;12. https://doi.org/10.3389/fphar.2021.644718
10. Cao S, Lin C, Liang S, Tan CH, Er Saw P, Xu X. Enhancing chemotherapy by RNA interference. BIO Integration. 2020;1(2):64–81. http://dx.doi.org/10.15212/bioi-2020-0003
11. Roscigno G, Scognamiglio I, Ingenito F, Chianese RV, Palma F, Chan A, et al. Modulating the crosstalk between the tumor and the microenvironment using siRNA: A flexible strategy for breast cancer treatment. Cancers. 2020;12(12):3744. https://doi.org/10.3390%2Fcancers12123744
12. Jiang Y, Huo S, Hardie J, Liang X-J, Rotello VM. Progress and perspective of inorganic nanoparticle-based siRNA delivery systems. Expert Opin Drug Deliv. 2016;13(4):547–59. https://doi.org/10.1517/17425247.2016.1134486
13. Binnemars‐Postma K, Bansal R, Storm G, Prakash J. Targeting the STAT6 pathway in tumor‐associated macrophages reduces tumor growth and metastatic niche formation in breast cancer. FASEB J. 2018;32(2):969–78. https://doi.org/10.1096/fj.201700629r
14. Song Y, Tang C, Yin C. Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic delivery of multi-functionalized nanoparticles to tumor-associated macrophages and breast cancer cells. Biomaterials. 2018;185:117–32. https://doi.org/10.1016/j.biomaterials.2018.09.017
15. Hwang HJ, Lee Y-R, Kang D, Lee HC, Seo HR, Ryu J-K, et al. Endothelial cells under therapy-induced senescence secrete CXCL11, which increases aggressiveness of breast cancer cells. Cancer Lett. 2020;490:100–10. https://doi.org/10.1016/j.canlet.2020.06.019
16. Vicentini FT, Borgheti-Cardoso LN, Depieri LV, Abelha TF, Petrilli R, Bentley MV. Delivery Systems and local administration routes for therapeutic siRNA. Pharm Res. 2013;30(4):915–31. https://doi.org/10.1007%2Fs11095-013-0971-1
17. Hattab D, Gazzali AM, Bakhtiar A. Clinical advances of siRNA-based nanotherapeutics for cancer treatment. Pharmaceutics. 2021;13(7):1009. https://doi.org/10.3390%2Fpharmaceutics13071009
18. Watts J, Deleavey G, Damha M. Chemically modified siRNA: Tools and applications. Drug Discov Today. 2008;13(19–20):842–55. https://doi.org/10.1016/j.drudis.2008.05.007
19. Layzer JM, McCafrey AP, Tanner AK, Huang Z, Kay MA, Sullenger BA. In vivo activity of nuclease-resistant siRNAs. RNA. 2004;10(5):766–71. https://doi.org/10.1261/rna.5239604
20. Damase TR, Sukhovershin R, Boada C, Taraballi F, Pettigrew RI, Cooke JP. The limitless future of RNA therapeutics. Front Bioeng Biotechnol. 2021;9. https://doi.org/10.3389/fbioe.2021.628137
21. Malburet C, Leclercq L, Cotte J-F, Thiebaud J, Bazin E, Garinot M, et al. Size and charge characterization of lipid nanoparticles for mRNA vaccines. Anal Chem. 2022;94(11):4677–85. https://doi.org/10.1021/acs.analchem.1c04778
22. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15(8):541–55. https://doi.org/10.1038/nrg3763
23. Couto LB, High KA. Viral vector-mediated RNA interference. Curr Opin Pharmacol. 2010;10(5):534–42. https://doi.org/10.1016/j.coph.2010.06.007
24. Kasar S, Salerno E, Yuan Y, Underbayev C, Vollenweider D, Laurindo MF, et al. Systemic in vivo lentiviral delivery of mir-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia. Genes & Immun. 2011;13(2):109–19. https://doi.org/10.1038/gene.2011.58
25. Lou W, Chen Q, Ma L, Liu J, Yang Z, Shen J, et al. Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model. J Mol Med. 2013;91(6):715–25. https://doi.org/10.1007/s00109-012-0985-x
26. Borel F, Kay MA, Mueller C. Recombinant AAV as a platform for translating the therapeutic potential of RNA interference. Mol Ther. 2014;22(4):692–701. https://doi.org/10.1038/mt.2013.285
27. Lam JK, Chow MY, Zhang Y, Leung SW. siRNA versus miRNA as therapeutics for gene silencing. Mol Ther Nucleic Acids. 2015;4(9). https://doi.org/10.1038%2Fmtna.2015.23
28. Chen Y, Zhu X, Zhang X, Liu B, Huang L. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther. 2010;18(9):1650–6. https://doi.org/10.1038/mt.2010.136
29. Pattni BS, Chupin VV, Torchilin VP. New developments in liposomal drug delivery. Chem Rev. 2015;115(19):10938–66. https://doi.org/10.1021/acs.chemrev.5b00046
30. Young SW, Stenzel M, Jia-Lin Y. Nanoparticle-siRNA: A potential cancer therapy? Crit Rev Oncol Hemato. 2016;98:159–69. https://doi.org/10.1016/j.critrevonc.2015.10.015
31. Tokatlian T, Segura T. siRNA applications in nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010;2(3):305–15. https://doi.org/10.1002/wnan.81
32. Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: Structure, preparation and application. Adv Pharm Bull. 2015;5(3):305–13. https://doi.org/10.15171%2Fapb.2015.043
33. Hoy SM. Patisiran: First global approval. Drugs. 2018;78(15):1625–31. https://doi.org/10.1007/s40265-018-0983-6
34. Ilarduya CT, Düzgüneş N, Sun Y. Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci. 2010;40(3):159-70. https://doi.org/10.1016/j.ejps.2010.03.019
35. Xin Y, Huang M, Guo WW, Huang Q, Zhang L Zhen, Jiang G. Nano-based delivery of RNAi in cancer therapy. Mol Cancer. 2017;16(1). https://doi.org/10.1186%2Fs12943-017-0683-y
36. Singh A, Trivedi P, Jain NK. Advances in siRNA delivery in cancer therapy. Artif Cells Nanomed Biotechnol. 2017;46(2):274–83. https://doi.org/10.1080/21691401.2017.1307210
37. Mao S, Sun W, Kissel T. Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev. 2010;62(1):12–27. https://doi.org/10.1016/j.addr.2009.08.004
38. Noh SM, Han SE, Shim G, Lee KE, Kim C-W, Han SS, et al. Tocopheryl oligochitosan-based self assembling oligomersomes for siRNA delivery. Biomaterials. 2011;32(3):849–57. https://doi.org/10.1016/j.biomaterials.2010.09.027
39. Şalva E, Özbaş S, Alan S, Özkan N, Ekentok‐Atıcı C, Kabasakal L, et al. Combination therapy with Chitosan/siRNA nanoplexes targeting PDGF‐D and pdgfr‐β reveals anticancer effect in breast cancer. J Gene Med. 2022;25(2). https://doi.org/10.1002/jgm.3465
40. Zhang S, Zhao B, Jiang H, Wang B, Ma B. Cationic lipids and polymers mediated vectors for delivery of siRNA. J Control Release. 2007;123(1):1–10. https://doi.org/10.1016/j.jconrel.2007.07.016
41. Urban-Klein B, Werth S, Abuharbeid S, Czubayko F, Aigner A. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther. 2004;12(5):461–6. https://doi.org/10.1038/sj.gt.3302425
42. Kim Y-K, Minai-Tehrani A, Lee, Cho C-S, Cho M-H, Jiang H-L. Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-PDCD4 complexes in H-RAS12V mice with liver cancer. Int J Nanomedicine. 2013;8: 1489-98. https://doi.org/10.2147/ijn.s42949
43. Johnson KS, Conant EF, Soo MS. Molecular subtypes of breast cancer: A review for Breast Radiologists. J Breast Imaging. 2020;3(1):12–24. http://dx.doi.org/10.1093/jbi/wbaa110
44. Ngamcherdtrakul W, Yantasee W. siRNA Therapeutics for breast cancer: Recent efforts in targeting metastasis, drug resistance, and immune evasion. Transl Res. 2019;214:105–20. https://doi.org/10.1016/j.trsl.2019.08.005
45. Ngamcherdtrakul W, Morry J, Gu S, Castro DJ, Goodyear SM, Sangvanich T, et al. Cationic polymer modified mesoporous silica nanoparticles for targeted siRNA delivery to HER2+ breast cancer. Adv Funct Mater. 2015;25(18):2646–59. https://doi.org/10.1002/adfm.201404629
46. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: Globocan sources and methods. Int J Cancer. 2018;144(8):1941–53. https://doi.org/10.1002/ijc.31937
47. Schultheis B, Strumberg D, Kuhlmann J, Wolf M, Link K, Seufferlein T, et al. Safety, efficacy and Pharcacokinetics of targeted therapy with the liposomal RNA interference therapeutic ATU027 combined with gemcitabine in patients with pancreatic adenocarcinoma. A randomized phase IB/IIA Study. Cancers. 2020;12(11):3130. https://doi.org/10.3390%2Fcancers12113130
48. Schultheis B, Strumberg D, Santel A, Vank C, Gebhardt F, Keil O, et al. First-in-human phase I study of the liposomal RNA interference therapeutic ATU027 in patients with advanced solid tumors. J Clin Oncol. 2014;32(36):4141–8. https://doi.org/10.1200/jco.2013.55.0376
49. Suraya A, Nowak D, Sulistomo AW, Icksan AG, Berger U, Syahruddin E, et al. Excess risk of lung cancer among agriculture and construction workers in Indonesia. Ann Glob Health. 2021;87(1):8. https://doi.org/10.5334%2Faogh.3155
50. Khan P, Siddiqui JA, Lakshmanan I, Ganti AK, Salgia R, Jain M, et al. RNA-based therapies: A cog in the wheel of lung cancer defense. Mol Cancer. 2021;20(1):54. https://doi.org/10.1186/s12943-021-01338-2
51. Pang L, Shah H, Wang H, Shu D, Qian SY, Sathish V. EPCAM-targeted 3WJ RNA nanoparticle harboring delta-5-desaturase siRNA inhibited lung tumor formation via DGLA peroxidation. Mol Ther Nucleic Acids. 2020;22:222–35. https://doi.org/10.1016/j.omtn.2020.08.024
52. Magalhães M, Alvarez-Lorenzo C, Concheiro A, Figueiras A, Santos AC, Veiga F. RNAi-based therapeutics for lung cancer: Biomarkers, micrornas, and nanocarriers. Expert Opin Drug Deliv. 2018;15(10):965–82. https://doi.org/10.1080/17425247.2018.1517744
53. Kara G, Calin GA, Ozpolat B. RNAi-based Therapeutics and tumor targeted delivery in cancer. Adv Drug Deliv Rev. 2022;182:114113. https://doi.org/10.1016/j.addr.2022.114113
54. Jiang Q, Wei H, Tian Z. Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway. BMC cancer. 2008. 8:12. https://doi.org/10.1186/1471-2407-8-12
55. Cunningham D, Salazar R, Sobrero A, Ducreux MP, Van Cutsem E, Scheithauer W, et al. Lefitolimod vs Standard of Care (SOC) for patients with metastatic colorectal cancer (mcrc) responding to first-line standard treatment: Results from the Randomized Phase III IMPALA trial. Ann Onc. 2019;30:v868–9. https://doi.org/10.1093/annonc%2Fmdz394.022
56. Kuźbicki Ł, Brożyna AA. Expression of cyclooxygenase-2 in human epithelial skin lesions. Appl Immunohistochem Mol Morphol. 2021. 29(3):163-174. https://doi.org/10.1097/pai.0000000000000871
57. Schultheis B, Strumberg D, Kuhlmann J, Wolf M, Link K, Seufferlein T, et al. Safety, efficacy and pharmacokinetics of targeted therapy with the liposomal RNA interference therapeutic ATU027 combined with gemcitabine in patients with pancreatic adenocarcinoma. A randomized phase IB/IIA Study. Cancers. 2020;12(11):3130. https://doi.org/10.3390/cancers12113130
58. Golan T, Khvalevsky EZ, Hubert A, Gabai RM, Hen N, Segal A, et al. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients. Oncotarget. 2015;6(27):24560–70. https://doi.org/10.18632/oncotarget.4183
59. Wolf D, Baier G. IFNγ helps CBLB-deficient CD8+ T cells to put up resistance to Tregs. Cancer Immunol Res. 2022;10(4):370–370. https://doi.org/10.1158/2326-6066.cir-22-0080
60. Reid G, Pel ME, Kirschner MB, Cheng YY, Mugridge N, Weiss J, et al. Restoring expression of miR-16: A novel approach to therapy for malignant pleural mesothelioma. Ann Oncol. 2013;24(12):3128–35. https://doi.org/10.1093/annonc/mdt412
61. Ganesh S, Cyr W, Koser M, Chopda G, Chipumuro E, Siddiquee Z, et al. Abstract 3827: Preclinical characterization of DCR-BCAT as a component of combination therapy. Cancer Res. 2016;76(14_Supplement):3827–3827. http://dx.doi.org/10.1158/1538-7445.AM2016-3827
62. Bianchi F, Alexiadis S, Camisaschi C, Truini M, Centonze G, Milione M, et al. TLR3 expression induces apoptosis in human non-small-cell lung cancer. Int J Mol Sci. 2020;21(4):1440. https://doi.org/10.3390%2Fijms21041440
63. Mitchell WM. Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Expert Rev Clin Pharmacol. 2016;9(6):755–70. https://doi.org/10.1586/17512433.2016.1172960
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